Flavonoid-rich fruit and vegetables improve microvascular reactivity and inflammatory status in men at risk of cardiovascular disease—FLAVURS: a randomized controlled trial12345

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ABSTRACT

Background:

Observed associations between increased fruit and vegetable (F&V) consumption, particularly those F&Vs that are rich in flavonoids, and vascular health improvements require confirmation in adequately powered randomized controlled trials.

Objective:

This study was designed to measure the dose-response relation between high-flavonoid (HF), low-flavonoid (LF), and habitual F&V intakes and vascular function and other cardiovascular disease (CVD) risk indicators.

Design:

A single-blind, dose-dependent, parallel randomized controlled dietary intervention study was conducted. Male and female low-F&V consumers who had a ≥1.5-fold increased risk of CVD (n = 174) were randomly assigned to receive an HF F&V, an LF F&V, or a habitual diet, with HF and LF F&V amounts sequentially increasing by 2, 4, and 6 (+2, +4, and +6) portions/d every 6 wk over habitual intakes. Microvascular reactivity (laser Doppler imaging with iontophoresis), arterial stiffness [pulse wave velocity, pulse wave analysis (PWA)], 24-h ambulatory blood pressure, and biomarkers of nitric oxide (NO), vascular function, and inflammation were determined at baseline and at 6, 12, and 18 wk.

Results:

In men, the HF F&V diet increased endothelium-dependent microvascular reactivity (P = 0.017) with +2 portions/d (at 6 wk) and reduced C-reactive protein (P = 0.001), E-selectin (P = 0.0005), and vascular cell adhesion molecule (P = 0.0468) with +4 portions/d (at 12 wk). HF F&Vs increased plasma NO (P = 0.0243) with +4 portions/d (at 12 wk) in the group as a whole. An increase in F&Vs, regardless of flavonoid content in the groups as a whole, mitigated increases in vascular stiffness measured by PWA (P = 0.0065) and reductions in NO (P = 0.0299) in the control group.

Conclusion:

These data support recommendations to increase F&V intake to ≥6 portions daily, with additional benefit from F&Vs that are rich in flavonoids, particularly in men with an increased risk of CVD. This trial was registered at www.controlled-trials.com as ISRCTN47748735.

Cited by (0)

1

From the Hugh Sinclair Unit of Human Nutrition (ALM, TWG, MFC, DSA, YJ, AV, JPES, OBK, KMT, A-MM, MHG, and JAL), and the Institute for Cardiovascular and Metabolic Research, Department of Food and Nutritional Sciences (ALM and JAL), University of Reading, Reading, Berkshire, United Kingdom.

2

ALM and TWG are joint first authors.

3

Present address: for TWG, Northumbria University, Faculty of Health and Life Sciences, Newcastle upon Tyne, United Kingdom; for KMT, Research and Innovation Centre, Fondazione Edmund Mach, San Michele all’Adige, Trento, Italy; for A-MM, Norwich Medical School, University of East Anglia, Norwich, United Kingdom; for MFC, Clinical Nutrition Research Centre, Singapore Institute for Clinical Sciences, Singapore.

4

Supported by the Food Standards Agency, United Kingdom (project no. N02039/F5234012). Sainsbury’s PLC (supermarket retailer) provided the study foods.

5

Address correspondence and requests for reprints to JA Lovegrove, Hugh Sinclair Unit of Human Nutrition, Department of Food and Nutritional Sciences, University of Reading, Reading, Berkshire RG6 6AP, United Kingdom. E-mail: [email protected].

6

Abbreviations used: ABP, ambulatory blood pressure; AIx, augmentation index; AUC, area under the flux versus time curve; BP, blood pressure; CRP, C-reactive protein; CVD, cardiovascular disease; DBP, diastolic blood pressure; DVP, digital volume pulse; eNOS, endothelial nitric oxide synthase; FLAVURS, FLAvonoids and Vascular function at the University of Reading Study; F&V, fruit and vegetable; HF, high-flavonoid; LDI, laser Doppler imaging with iontophoresis; LF, low-flavonoid; NO, nitric oxide; PWA, pulse wave analysis; PWV, pulse wave velocity; SBP, systolic blood pressure; SNP, sodium nitroprusside; VCAM, vascular cell adhesion molecule.